Aliphatic propargylamines as cellular rescue agents

Abstract

The present invention relates to the use of a group of propargylamines of the general formula (I) ##STR1## wherein R 1 is hydrogen or CH 3 and R 2 is (CH 2 ) n CH 3 and n is an integer from 0 to 16, and salts thereof, as cellular rescue agents in the treatment and prevention of diseases in which cell death occurs by apoptosis. Some of the compounds of formula I are novel. The invention is also directed to the use of these compounds in the treatment of these diseases, as well as to processes for the preparation of the compounds.

We claim: 
     
       1. A compound having the formula I: ##STR14## wherein R 1  =H, CH 3  ; R 2  =CH 3  (CH 2 ) n  ; and n represents an integer in the range from 0 to 16, with the provisos that:     (i) if R 1  is H, then n is not 4 or less;   (ii) if R 1  is CH 3 , then n is not 0; and   (iii) if R 1  is CH 3  and n is 1 or 4, then the compound of formula (I) is in the form of a substantially pure enantiomer; or a pharmaceutically acceptable salt thereof.     
     
     
       2. A compound according to claim 1 in which R 1  differs from R 2 , as a substantially pure enantiomer in the R-configuration. 
     
     
       3. A compound according to claim 1 in which R 1  differs from R 2 , as a substantially pure enantiomer in the S-configuration. 
     
     
       4. A compound according to claim 1, wherein said compound of formula (I) is selected from the group consisting of: (R)-N-(2-butyl)propargylamine;   (R)-N-(2-pentyl)propargylamine;   (R)-N-(2-hexyl)propargylamine;   (R)-N-(2-heptyl)propargylamine;   (R)-N-(2-octyl)propargylamine;   (R)-N-(2-nonyl)propargylamine;   (R)-N-(2-decyl)propargylamine;   (R)-N-(2-undecyl)propargylamine;   (R)-N-(2-dodecyl)propargylamine; or a pharmaceutically acceptable salt thereof.     
     
     
       5. A compound according to claim 1, wherein said compound of formula (I) is selected from the group consisting of: (S)-N-(2-butyl)propargylamine;   (S)-N-(2-pentyl)propargylamine;   (S)-N-(2-hexyl)propargylamine;   (S)-N-(2-heptyl)propargylamine;   (S)-N-(2-octyl)propargylamine;   (S)-N-(2-nonyl)propargylamine;   (S)-N-(2-decyl)propargylamine;   (S)-N-(2-undecyl)propargylamine;   (S)-N-(2-dodecyl)propargylamine; or a pharmaceutically acceptable salt thereof.     
     
     
       6. A compound according to claim 1, wherein said compound of formula (I) is selected from the group consisting of: N-(1-heptyl)propargylamine;   N-(1-octyl)propargylamine;   N-(1-nonyl)propargylamine;   N-(1-decyl)propargylamine;   N-(1-undecyl)propargylamine;   N-(1-dodecyl)propargylamine; or a pharmaceutically acceptable salt thereof.     
     
     
       7. A compound according to claim 1 in the form of the hydrochloride salt. 
     
     
       8. A compound according to claim 1 wherein n is an integer from 1 to 12. 
     
     
       9. A compound according to claim 1 wherein n is an integer from 1 to 9.